Newly diagnosed cardiovascular disease in patients treated with immune checkpoint inhibitors: a retrospective analysis of patients at an academic tertiary care center.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune-related adverse events including cardiotoxicity. We estimated the incidence of newly diagnosed cardiovascular disease in patients treated with ICIs at a large, tertiary care center. METHODS: All patients with a cancer diagnosis who received any ICI treatment in the University of Florida's Integrated Data Repository from 2011 to 2017 were included. Cardiovascular disease was defined as a new ICD diagnosis code for cardiomyopathy, heart failure, arrhythmia, heart block, pericardial disease, or myocarditis after initiation of ICI treatment. RESULTS: Of 102,701 patients with a diagnosis of malignancy, 424 patients received at least one ICI. Sixty-two (14.6%) patients were diagnosed with at least one new cardiovascular disease after initiation of ICI therapy. Of the 374 patients receiving one ICI, 21 (5.6%) developed heart failure. Of the 49 patients who received two ICIs sequentially, three (6.1%) developed heart failure and/or cardiomyopathy. Incident cardiovascular disease was diagnosed at a median of 63 days after initial ICI exposure. One patient developed myocarditis 28 days after receiving nivolumab. Mortality in ICI treated patients with a concomitant diagnosis of incident cardiovascular disease was higher compared to those who did not (66.1% vs. 41.4%, odds ratio = 2.77, 1.55-4.95, p = 0.0006). CONCLUSIONS: This study suggests a high incidence of newly diagnosed cardiovascular disease after the initiation of ICI therapy in a real-world clinical setting.

Prescribing Prevalence of Medications With Potential Genotype-Guided Dosing in Pediatric Patients.

Importance: Genotype-guided prescribing in pediatrics could prevent adverse drug reactions and improve therapeutic response. Clinical pharmacogenetic implementation guidelines are available for many medications commonly prescribed to children. Frequencies of medication prescription and actionable genotypes (genotypes where a prescribing change may be indicated) inform the potential value of pharmacogenetic implementation. Objective: To assess potential opportunities for genotype-guided prescribing in pediatric populations among multiple health systems by examining the prevalence of prescriptions for each drug with the highest level of evidence (Clinical Pharmacogenetics Implementation Consortium level A) and estimating the prevalence of potential actionable prescribing decisions. Design, Setting, and Participants: This serial cross-sectional study of prescribing prevalences in 16 health systems included electronic health records data from pediatric inpatient and outpatient encounters from January 1, 2011, to December 31, 2017. The health systems included academic medical centers with free-standing children's hospitals and community hospitals that were part of an adult health care system. Participants included approximately 2.9 million patients younger than 21 years observed per year. Data were analyzed from June 5, 2018, to April 14, 2020. Exposures: Prescription of 38 level A medications based on electronic health records. Main Outcomes and Measures: Annual prevalence of level A medication prescribing and estimated actionable exposures, calculated by combining estimated site-year prevalences across sites with each site weighted equally. Results: Data from approximately 2.9 million pediatric patients (median age, 8 [interquartile range, 2-16] years; 50.7% female, 62.3% White) were analyzed for a typical calendar year. The annual prescribing prevalence of at least 1 level A drug ranged from 7987 to 10 629 per 100 000 patients with increasing trends from 2011 to 2014. The most prescribed level A drug was the antiemetic ondansetron (annual prevalence of exposure, 8107 [95% CI, 8077-8137] per 100 000 children). Among commonly prescribed opioids, annual prevalence per 100 000 patients was 295 (95% CI, 273-317) for tramadol, 571 (95% CI, 557-586) for codeine, and 2116 (95% CI, 2097-2135) for oxycodone. The antidepressants citalopram, escitalopram, and amitriptyline were also commonly prescribed (annual prevalence, approximately 250 per 100 000 patients for each). Estimated prevalences of actionable exposures were highest for oxycodone and ondansetron (>300 per 100 000 patients annually). CYP2D6 and CYP2C19 substrates were more frequently prescribed than medications influenced by other genes. Conclusions and Relevance: These findings suggest that opportunities for pharmacogenetic implementation among pediatric patients in the US are abundant. As expected, the greatest opportunity exists with implementing CYP2D6 and CYP2C19 pharmacogenetic guidance for commonly prescribed antiemetics, analgesics, and antidepressants.

Postnatal pediatric systemic antibiotic episodes during the first three years of life are not associated with mode of delivery.

BACKGROUND: Delivery by cesarean section (C-section) is associated with adverse short-term and long-term infant outcomes. Given that antibiotics during early life are prescribed for infant outcomes that are more likely among c-section deliveries, we hypothesized that postnatal antibiotic exposure will be greater among c-section infants compared to vaginally delivered infants. OBJECTIVE: The aim of this paper was to evaluate if mode of infant delivery was associated with patterns of systemic antibiotic exposure in children during their first three years. METHODS: Pediatric electronic health records from UFHealth, 2011 to 2017 were reviewed. We included singleton, term infants (37-42 weeks gestation) with a birth weight ≥ 2500 grams, with documented mode of delivery and well visits on record. Infants with a neonatal intensive care unit stay were excluded. Both oral and intravenous antibiotics for a 10-day duration were classified as a single episode. The primary outcome was antibiotic episodes in the first three years of life, and a sub-analysis was performed to compare broad-spectrum versus narrow-spectrum antibiotic exposures. RESULTS: The mean number of antibiotic episodes in 4,024 full-term infants was 0.34 (SD = 0.79) and 24.1% of infants had at least one antibiotic episode. Penicillins were the most prescribed antibiotic in children 0-1 years (66.9%) and cephalosporins were the most common antibiotic prescribed for children 1-3 years (56.2%). We did not detect a meaningful or significant rate ratio (RR) between mode of delivery and overall antibiotic episodes 1.14 (95% CI 0.99, 1.31), broad-spectrum episodes 1.19 (95% CI 0.93, 1.52, or narrow-spectrum episodes 1.14 (95% CI 0.97, 1.34). CONCLUSION: Our results do not support the hypothesis that postnatal antibiotic exposure was greater among infants delivered by cesarean section compare to infants delivered vaginally during the first three years of life.

Hourly Effect of Pretreatment With IV Antibiotics on Blood Culture Positivity Rate in Emergency Department Patients.

Although it is intuitive that antibiotics administered before obtaining a blood culture would reduce the likelihood of obtaining a positive culture, it is not clear exactly how rapidly and to what extent blood becomes sterile after administration of intravenous (IV) antibiotics. Using a large data set of patients admitted from the UFHealth Shands Adult Emergency Department (ED) between 2012 and 2016 (n = 25 686), we had the opportunity to more closely examine the effect of starting IV antibiotics before vs after obtaining blood cultures. We present data on the effect of pretreatment with IV antibiotics for both septic and nonseptic ED patients on the blood culture positivity rate on an hour-by-hour basis, as well as the effects on distribution of species recovered and the impact of antibiotic resistance in empiric treatment with antibiotics.

Relationship between bacteriology report time in the morning and length of stay in hospital after the report.

We studied the relationship between the time of day bacteriology reports were available in the electronic medical record (Epic, Verona, WI) and subsequent length of stay (LOS) following the last report before discharge. All patients ≥18years admitted to the UF Health Shands Hospital between 1/1/2014-2/29/2016 were included. We calculated the mean LOS following the report for each half-hour time period between 6AM and 1PM (N=14, 95.6% of all results) and tested the relationship to subsequent LOS. For patients whose total LOS was ≤168hours (N=13,830) there was a highly significant positive linear relationship between the report time and LOS following the last report (r=0.8813, P=0.00001556). For those patients with total LOS>168h, there was no clear relationship between report time in the morning and LOS after the last bacteriology report. The relationship between bacteriology report time in the morning and use of this information by physicians in discharge decision-making is likely to be complex and multi-factorial, but for those patients with a total hospital LOS ≤168h, there is a strong relationship between an earlier report and earlier patient discharge.

Consent2Share: an integrated broad consenting process for re-contacting potential study subjects.

Background and Aim: Obtaining sufficient subjects into research studies is an ongoing barrier to conducting clinical research. Privacy rules add to the complexity of identifying qualified study subjects. The process described facilitates consent of patients coming to their clinically scheduled appointments who are asked to consent to having researchers review their electronic medical records (EHR), and if they meet study criteria for future research, being contacted by those researchers and asked if they wish to be involved in a research project. Methods: An interdisciplinary group representing the Institutional Review Board (IRB), Information Technology (IT), Hospital, University and Research developed an initial paper then electronic method to consent all patients attending a medical subspecialty clinic. All consent data are integrated to the EHR to facilitate linking to clinical information. Results: Although the paper consenting method resulted in over an 80% "yes" rate of consent, it was complicated by significant procedural challenges which prevented scalability. Revising the process has resulted in nearly 28,000 patients consenting in a 3 year period and in 20 IRB approved protocols using subjects who agreed to Consent2Share. Conclusions: A multi-disciplinary effort is essential to develop a successful electronic based, integrated process to assist investigators and patients to facilitate study subject accrual. Relevance for patients: Consent2Share more efficiently assists researchers in identifying and contacting potential study subjects that meet entrance criteria. The process provides a model to comply with the proposed Notice of Public Rule Making (NPRM) where institutions will be strongly encouraged to develop broad research consent procedures.